Quadrivalvular rheumatic heart disease

Three cases of chronic rheumatic heart disease with involvement of all four valves are presented. The involvement of tricuspid and pulmonary valves was suspected clinically and was confirmed by two-dimensional echo, Doppler, hemodynamic and angiographic findings. These findings were also verified surgically and histopathologically in 2 cases. One of the cases died after cardiac catheterization; the other 2 cases were treated surgically with success.     

Interleukin-4 as a potent down-regulator for human alveolar macrophages capable of producing tumour necrosis factor-alpha and interleukin-1.

The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha.     

Prognosis of trochanteric pain in primary care

BACKGROUND: Trochanteric pain is the second most important diagnosis of hip problems presenting in primary care, but its incidence and prognosis in this context is largely unknown. AIM: To determine the 1- and 5-year prognoses of trochanteric pain and the predictive variables for consistent complaints. DESIGN OF THE STUDY: Retrospective cohort study. SETTING: One hundred and sixty-four patients (mean age = 55 years, 80% female) with incidental trochanteric pain in the years 1996 or 2000 were asked in 2001 for past and present symptoms of trochanteric pain. Therapeutic interventions, demographic factors and comorbidity were also investigated. METHOD: The databases of 39 GPs were screened in order to identify all incident cases with a suspicion of trochanteric pain in the years 1996 or 2000. These cases were sent a questionnaire. RESULTS: The incidence of trochanteric pain in primary care is 1.8 patients per 1000 per year. After 1 year at least 36% still suffered from trochanteric pain, and after 5 years this was 29%. Patients with osteoarthritis (OA) in the lower limbs had a 4.8-fold risk of persistent symptoms after 1 year, as compared to patients without OA. Patients who had received a corticosteroid injection had a 2.7-fold chance of recovery after 5 years, as compared with patients who had not received an injection. CONCLUSION: Trochanteric pain is shown to be a chronic disease in a substantial number of patients. The disorder is associated with much impairment when conducting daily activities.     

The whole leg radiograph

The whole leg radiograph (WLR), the standard technique for determining axial alignment, is usually taken in a standing position, although some prefer the supine position. To determine the difference between these two positions, we performed a standing and a supine WLR in 20 patients with a varus alignment. We found an average of 2 degrees more varus deviation in the standing position than in the supine position.     

Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms: data from seroconverters in the CASCADE collaboration from 1987 to 2003

OBJECTIVES: To examine factors influencing the rate of transmitted drug resistance (TDR) among seroconverters, with particular emphasis on 3 widely used genotypic drug resistance algorithms. METHODS: The study used data from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration of seroconverter cohorts in Europe and Canada. Genotypic resistance data were derived within 18 months of the last seronegative test or date of laboratory evidence of acute infection and before the initiation of antiretroviral therapy. The Stanford algorithm was used to analyze each individual's nucleotide sequence. A multivariate logistic model was used to assess independent relationships between the presence of TDR and exposure category, sex, age at seroconversion, and year of seroconversion. The paper also describes 3 alternative definitions of resistance: the Stanford algorithm, the key resistance mutations defined by the International AIDS Society, and the Agence Nationale de Recherches sur le Sida (ANRS) algorithm. RESULTS: Forty-five of 438 patients (10.3%) seroconverting between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty patients (9.1%) showed resistance mutations to only 1 class of antiretroviral drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral therapy. It was suggested that individuals seroconverting later in calendar time were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003, respectively, compared with pre-1996; P trend = 0.08). This trend was apparent regardless of the definition of TDR used. The total estimated proportion of individuals with TDR varied between 10.3% and 15.5% according to which definition was used. CONCLUSIONS: Evidence was found for the rise of TDR over time. A specific definition of what constitutes TDR rather than a simple list of mutations is needed.     

Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells

The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.     

Fas-mediated apoptosis of neutrophils in sera of patients with infection

In the presence of infection, neutropenia is considered to be a marker of poor prognosis; conversely, neutrophilia may not be a determinant of a better prognosis. Since apoptotic neutrophils are compromised functionally, we evaluated the effect of infection on neutrophil apoptosis. The rate of apoptosis was greater for neutrophils isolated from patients with infection than for healthy controls. Escherichia coli did not directly modulate the rate of neutrophil apoptosis. However, sera from infected patients promoted (P < 0.001) neutrophil apoptosis. Interestingly, the sera of patients with different types of infection (gram negative, gram positive, or culture negative) exerted a more or less identical response on neutrophil apoptosis. Sera of infected patients showed a fivefold greater content of FasL compared to controls. Moreover, anti-FasL antibody partly attenuated the infected-serum-induced neutrophil apoptosis. In in vitro studies, E. coli enhanced monocyte FasL expression. Moreover, conditioned media prepared from activated macrophages from control mice showed enhanced apoptosis of human as well as mouse neutrophils. On the contrary, conditioned media prepared from activated macrophages isolated from FasL-deficient mice induced only a mild degree of neutrophil apoptosis. These results suggest that neutrophils in patients with infection undergo apoptosis at an accelerated rate. Infection not only promoted monocyte expression of FasL but also increased FasL content of the serum. Because the functional status of apoptotic cells is compromised, a significant number of neutrophils may not be participating in the body's defense. Since neutrophils play the most important role in innate immunity, their compromised status in the presence of infection may transfer the host defense burden from an innate response to acquired immunity. The present study provides some insight into the lack of correlation between neutrophilia and the outcome of infection.     

Decision and forecast horizons in a stochastic environment: A survey

This paper constructs a unified framework to survey most of the work done to date on decision

1 decision horizon replaces the term planning horizon used in the literature in the context of this paper. This is done because of an alternate and more popular use of the term planning horizon as simply the given length of the horizon in a finite horizon problem.

and forecast horizons in a stochastic environment. The paper is divided into sections by type of model. For each model type, the issues of existence of these horizons and of derivation of sufficient conditions for their determination are studied. Appropriate examples are presented.     

Structural spinal abnormalities on MRI and associations with weight status in a general pediatric population

BACKGROUND CONTEXTSeveral spinal abnormalities have been studied using magnetic resonance imaging (MRI). However, in children these studies were sparsely performed in general populations. Examining young children's spines is important since the shape of the bone is largely determined during the growth spurt. Furthermore, it is so far unknown if associations between weight status and spinal abnormalities, which are known for adolescents and adults, are already present in young children.PURPOSEWe aimed to present the prevalence of structural abnormalities in the prepubertal pediatric spine on MRI and their association with measures of the children's body weight and body composition.STUDY DESIGNCross-sectional study embedded in a prospective population-based birth cohort study.PATIENT SAMPLEFor this study, participants from the Generation R Study were selected based on the availability of MRI data of the lumbar spine and accelerometry data at the age of 9 years.OUTCOME MEASURESThe presence of structural abnormalities of intervertebral discs and vertebrae was scored on MRI. The body mass index-standard deviation [BMI-SD] score was calculated from objectively measured weight and height, and body composition measurements were obtained by a dual-energy X-ray absorptiometry scan.METHODSA semiquantitative scoring tool to assess the intervertebral discs and vertebrae of the lumbar spine on conventional MRI was designed for this purpose. Proportions of children with spinal abnormalities on at least one lumbar vertebral level were presented. Logistic regression was used to analyze associations between abnormalities and weight and body composition. We declare not to have any financial conflicts of interests.RESULTSWe included 559 children (median age of 9.88 years (interquartile range 6.74–10.02), 48.5% boys). Most frequently observed abnormalities of the intervertebral discs were abnormal signal intensity (24.9%), decreased or collapsed disc height (37.6%), disc bulging (73.3%), and abnormal nuclear shape (29.1%). Vertebral endplate irregularities and lumbosacral transitional vertebrae were seen in respectively 40% and 9.3% of the participants. Except for disc bulging, all abnormalities were predominantly present at the L5 level. Only the presence of endplate irregularities was associated with a higher body weight (BMI SD score (odds ratio [OR] 1.50 [95% confidence interval [CI] 1.21–1.86]) and BMI SD change (OR 1.48 [95% CI 1.07–2.03])) and increased body mass values in body composition measurements (% body fat (OR 1.05 [95% CI 1.02–1.09), fat mass index (OR 1.23 [95% CI 1.09–1.39]), and fat-free mass index (OR 1.30 [95% CI 1.06–1.59])) in adjusted analyses.CONCLUSIONSStructural spinal abnormalities, especially disc bulging, endplate irregularities, and an abnormal disc height, are already present in children aged 9 years from a Dutch population-based cohort. Of those abnormalities, endplate irregularities are associated with various weight and body composition measurements.